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Mol Biol Cell. 2012 Aug;23(15):2943-54. Epub 2012 Jun 6.

Nuclear hormone receptor corepressor promotes esophageal cancer cell invasion by transcriptional repression of interferon-γ-inducible protein 10 in a casein kinase 2-dependent manner.

Author information

1
Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2α phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser-2436 to stabilize the NCoR against the ubiquitin-dependent proteasomal degradation pathway. Importantly, NCoR promoted the invasion of esophageal cancer cells in a CK2-dependent manner. By using cyclic DNA microarray analysis, we identified CXCL10/IP-10 as a novel CK2α-NCoR cascade-regulated gene. The depletion of both NCoR and HDAC3 commonly derepressed IP-10 transcription, demonstrating the functional engagement of the NCoR-HDAC3 axis in IP-10 transcriptional repression. Furthermore, chromatin immunoprecipitation assays showed that c-Jun recruits NCoR-HDAC3 corepressor complexes to the (AP1 site of IP-10, leading to histone hypoacetylation and IP-10 down-regulation. Collectively these data suggest that the CK2α-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells.

PMID:
22675025
PMCID:
PMC3408420
DOI:
10.1091/mbc.E11-11-0947
[Indexed for MEDLINE]
Free PMC Article

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